The invention relates to a method for measuring nitric oxide (NO) concentration in exhaled air, in which method the exhaled air is blown through a blow tube in measuring equipment, and nitric oxide concentration is measured in the exhaled air flowing in the blow tube. Further, the invention relates to measuring equipment for measuring the nitric oxide concentration of exhaled air, the measuring equipment comprising a blow tube, through which the exhaled air is blown and a measuring means for measuring the nitric oxide concentration of the exhaled air flowing through the blow tube.
Nitric oxide is a gaseous molecule that is intrinsically easily reactive. It also acts in the body as a signaling molecule that has various physiological and pathophysiological functions. For instance, nitric oxide regulates the function of respiratory organs in various conditions both in normal physiological and inflammatory states. Even though nitric oxide is easily reactive, some of the nitric oxide produced in the lungs mixes with pulmonary air and minor amounts of nitric oxide can be measured in exhaled air. In inflammatory lung diseases, such as asthma and alveolitis, the nitric oxide concentration of the exhaled air is higher than normal, since the nitric oxide concentration has increased because of the inflammation. So, the nitric oxide concentration can be used as an indicator of an inflammation in the lungs and of inflammatory diseases.
The nitric oxide concentration of exhaled air can be measured by an analyzer intended for that purpose. Currently, analyzers based on ozone chemiluminescence technology are commercially available on the market. In known measuring methods, a person to be examined exhales the exhalation air into an analyzer such that the flow rate of the exhaled air remains substantially constant. By this measuring method it is possible to detect a rise in the nitric oxide concentration of the exhaled air and thus to conclude, on the basis of the increased nitric oxide concentration, that there is inflammation in the lungs, but in which part of the lungs said inflammation is located cannot be found out by this method.
Mathematical models on pulmonary NO dynamics have been published during the past few years, in which models the lungs are divided into two compartments, i.e. a bronchial compartment and an alveolar compartment. On the basis of these models it is possible to calculate separately bronchial NO flux and correspondingly alveolar NO concentration. On the basis of these parameters, it is possible to assess in which lung compartment according to the model the nitric oxide production has increased and/or the nitric oxide diffusion has changed, and hence it can be determined relatively reliably, in which lung compartment according to the model inflammation may be located.
In known nitric oxide measuring devices a predetermined exhalation flow rate can be provided by devices with known flow resistance, and during the measurement, the aim is to keep the exhalation flow rate desired by keeping the exhalation pressure constant. In these known solutions the patient monitors the exhalation pressure value either with a separate pressure gauge or on the computer display and tries to keep the pressure at a predetermined pressure value as constant as possible during the whole exhalation. Another measuring method is to use a flow rate meter, whereby the person to be measured monitors the flow rate and attempts to keep it as steady as possible and at a predetermined value. The prior art has a problem that the result depends on the ability of the person to be measured to keep his/her exhalation flow rate constant by monitoring the exhalation pressure or exhalation flow rate on the display. A problem with this technique is that the nitric oxide concentration of exhaled air changes greatly as the exhalation flow rate changes, and thus even a slight error or minor variations in the exhalation flow rate cause a considerable error in the measurement result of nitric oxide concentration.
In connection with the measurement, it should also be taken into account that very large amounts of nitric oxide are produced in the nasal cavity and in paranasal sinuses as compared with lower airways. In order that the measurement of nitric oxide concentration in the lungs could be carried out reliably from the exhaled air blown through the mouth, it must be made sure that no considerable amounts of nitric-oxide-containing air from the nasal cavity can be mixed with the air blown out from the lungs. This can be achieved by exhaling against a minor pressure during the nitric oxide measurement, whereby the soft palate closes the connection between the nasopharynx and the oral cavity preventing the above-mentioned airs from being mixed together. This can be achieved by a counter pressure of about 5 cm H2O.
The object of the present invention is to provide a method and measuring equipment, by which production and diffusion of nitric oxide in various parts of the lungs can be assessed more reliably and readily than before.
The method of the invention is characterized in that during exhalation the flow rate of the air flowing through a blow tube is measured and the flow resistance of the blow tube is adjusted on the basis of the measured flow rate value such that the flow rate of the exhaled air substantially remains at a predetermined flow rate value.
One preferred embodiment of the method according to the invention is characterized in that at least two different flow rate values are set for the exhaled air during the measurement, that the flow resistance of the blow tube is adjusted such that the flow rate of the exhaled air flowing through the blow tube sets in sequence either to one or more predetermined flow rates and that the nitric oxide concentration of the exhaled air is measured at each flow rate.
A second preferred embodiment of the method according to the invention is characterized in that the measured nitric oxide concentrations of the exhaled air are expressed proportional to the exhalation flow rate.
Measuring equipment of the invention, in turn, is characterized by comprising a flow sensor for measuring air flow rate and a flow resistance adjuster for adjusting the flow rate of exhaled air flowing through said tube to be substantially of predetermined magnitude during the measurement.
One preferred embodiment of the measuring equipment of the invention is characterized by comprising control means for setting the flow rate of exhaled air in sequence to at least two different flow rate values and for measuring the nitric oxide concentration from the exhaled air at each flow rate value during either one or more exhalations.
A second preferred embodiment of the measuring equipment of the invention is characterized in that the control means comprise a computer, to which are connected a measuring means for measuring the nitric oxide concentration and a flow meter, and which is correspondingly connected to control the flow adjuster for performing the measuring process preprogrammed in the computer on the basis of the preset air flow rate values.
A third preferred embodiment of the measuring equipment of the invention is characterized in that the flow meter is a mass flow meter and the flow adjuster is a mechanical, electrically controlled throttle.
The basic idea of the invention is that, during exhalation, exhalation flow rate is measured and controlled such that the flow rate remains substantially at a predetermined value while nitric oxide concentration of the air flowing out at said predetermined flow rate is measured. Further, the basic idea of the invention is that the air flow exhaled through the blow tube of the measuring equipment is adjusted by setting a plurality of different, predetermined flow rate values for it and the nitric oxide concentration of the exhaled air is measured at each preset flow rate value. According to one preferred embodiment of the invention, both the air flow rate adjustment and the nitric oxide concentration measurement at each set value are performed automatically during one or more exhalations.